The mitochondrial ADPR link between Ca 2+ store release and Ca 2+ influx channel opening in immune cells

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Abstract
The regulation of non‐voltage‐operated Ca 2+ channels in the plasma membrane remains unclear (1–3). However, there is often a link between the physiological release of Ca 2+ from intracellular stores and opening of Ca 2+ influx channels on the plasma membrane. This route has been referred to variouslyas store‐operated Ca 2+ entry (SOC), capacitative Ca 2+ entry, and Ca 2+ release‐activated channel opening (CRAC), and often underlies the large changes in cytosolic free Ca 2+ that accompany many stimuli in a wide variety of cell types (1–3). The linkage between Ca 2+ store release and opening of Ca 2+ channels on the plasma membrane has remained elusive for a number of years, perhaps in part because different mechanisms exist for this linkage, and are used to differing extents by different cells. We suggest here that one of the mechanisms that may operate in cells of the immune system, but that may be important elsewhere, involves the release of mitochondrial adenosine diphosphate ribose (ADPR) or nicotinamide adenine dinucleotide (NAD + ). There is accumulating evidence to support each of the steps necessary for a complete description of this “Ca 2+ store release to plasma membrane channel opening” link, but to our knowledge they have not been connected before to make a coherent model.—Ayub, K., Hallett, M. B. The mitochondrial ADPR link between Ca 2+ store release and Ca 2+ influx channel opening in immune cells. FASEB J. 18, 1335‐1338 (2004)

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